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24 cases of growth hormone(GH)-producing pituitary adenomas were studied with electron microscopy and immunoelectron microscopy by protein A-gold complex, 6 cases were identified as densely granulated GH adenoma and 15 cases as sparsely granulated GH adenoma, among which 4 cases were proved by immunoelectron microscopy to be containing granules with prolactin(PRL) activity simultaneously. Intracytoplasmic fibrous bodies were often seen in the sparsely granulated cells anyhow, not all those cells with fibrous bodies possess the secretory granules with GH activity, and fibrous bodies were also detected in some PRL cells of certain mixed type adenoma. This suggests that fibrous bodies might not be the specific morphological feature of pituitary growth hormone cell adenomas. 相似文献
3.
A 76-year-old woman presented with enlargement and weakness of her hands and feet coarsening of facial features, proximal
muscle weakness, and worsening of her noninsulindependent diabetes mellitus. Serum growth hormone, somatomedin-C, and prolactin
levels were elevated. Thyroid function test results and serum cortisol and adrenocorticotropic hormone levels were within
normal limits. Luteinizing and follicle-stimulating hormone levels were both low, suggesting possible partial hypopituitarism.
Magnetic resonance imaging of the sella demonstrated a pituitary lesion that measured 2.2 x 1 x 0.5 cm; it partially obliterated
the suprasellar cistern and it distorted the optic chiasm. Light microscopic and ultrastructural examination of the trans-sphenoidally
resected tissues identified characteristic features of 2 discrete pituitary adenomas that were in close apposition, but they
were sharply demarcated. The 2 components were a corticotroph adenoma and a sparsely granulated somatotroph adenoma. Multiple
adenomas of the pituitary are not rare; however, the majority are endocrinologically “nonfunctional.” We report a patient
with clinical features of acromegaly whose tumor was a composite lesion: one area exhibited morphological characteristics
of a corticotroph adenoma and another distinct area exhibited features of a somatotroph adenoma. The possible histogenesis
is discussed. 相似文献
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Toru Kameya M.D. Masaru Tsumuraya Isamu Adachi Kaoru Abe Kiyoshi Ichikizaki Shigeo Toya Reiko Demura 《Virchows Archiv : an international journal of pathology》1980,387(1):31-46
Summary Fifteen cases of pituitary adenoma, 14 of which were associated with hyperprolactinemia, were studied by observation and granule morphometry of electron micrographs, immunohistochemistry and sequential observation of in vitro release with regard to hormone production, storage and secretion. Adenoma cells of 6 cases with marked elevation of plasma prolactin were sparsely granulated, showed characteristic ultrastrucures including the presence of small secretory granules, well developed Golgi and rough membranes, misplaced exocytosis, and positive or negative immunostaining for prolactin. These adenomas also showed vigorous release of the hormone into the circulation and/or culture medium. In vitro studies showed that negative immunostaining of adenoma cells did not preclude the production and secretion of the hormone. One densely granulated adenoma containing cells with numerous lactotroph type granules showed moderate release of prolactin into the circulation. In an acromegalic case associated with both high plasma growth hormone and prolactin, some cells were shown by immunohistochemistry to store both hormones. There were 4 adenomas which could not be shown to produce, store and secrete prolactin by any method available.Abbreviations Used in this Paper ACTH
adrenocorticotropic hormone
-
-MSH
-melanocyte stimulating hormone
- hGH
human growth hormone
- hPRL
human prolactin
- LH
luteinizing hormone
- FSH
follicle stimulating hormone
- TSH
thyroid stimulating hormone
- TRH
Thyrotropin-releasing hormone
This work was supported in part by Grants-in-Aid for Cancer Research (No. 50-14) and for Specific Diseases (Disorder of Hypothalamic and Pituitary System) from the Ministry of Health and Welfare, and for Cancer Research (No. 401034) from the Ministry of Education, Science and Culture, Japan 相似文献
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The Immunophenotype of Pituitary Adenomas 总被引:2,自引:0,他引:2
Although the production of pituitary hormones by adenohypophysial tumors has been studied extensively, an examination of the
immunophenotype of pituitary adenomas using a broad spectrum of antibodies has not been previously investigated. We studied
23 pituitary adenomas using a large panel of antibodies to determine if these tumors exhibited a common immunophenotype. Various
neuroendocrine markers, synaptophysin, neuron-specific enolase (NSE), and the intermediate filament protein, low-mol-wt keratin
were expressed in most examples. There was, however, differential expression of chromogranin A in that few prolactin (PRL)
and adenocorticotrophic hormone (ACTH) adenomas stained positively, whereas all other adenoma subtypes were reactive. The
ACTH adenomas had a unique profile with positive staining for galanin, neurophysin, vasopressin, and ubiquitin. These results
indicate that (1) pituitary adenomas do not express a single “generic” immunophenotype; (2) synaptophysin is the most reliable
and best broad spectrum marker for pituitary adenomas; (3) the neuroendocrine granule marker chromogranin A is useful in the
identification of null cell adenoma, a tumor that usually does not stain for anterior pituitary tumors; and (4) among pituitary
tumors, ACTH adenomas have a unique immunoprofile. 相似文献
8.
The effects of somatostatin or the somatostatin analog SMS 201–995 were studied on 4 densely granulated somatotroph adenomas
and 4 sparsely granulated somatotroph adenomas in vitro. Release of growth hormone (GH) into culture media during incubation
with somatostatin or SMS 201 -995 were measured by radioimmunoassay, and light-microscopical and ultrastructural morphometric
parameters were compared with those of cultured control somatotroph adenoma cells of the same tumor. In all tumors except
for 1 densely granulated somatotroph adenoma, somatostatin or SMS 201–995 decreased GH release into culture media in 24- and
2-hour incubations. After 48-hour incubation with somatostatin or SMS 201–995, there was no change in cell size or secretory
granule diameter. One densely granulated adenoma showed decreased cytoplasmic volume density (CVD) of Golgi apparatus and
secretory granules, and a sparsely granulated adenoma had reduced CVD of endoplasmic reticulum. All the tumors that responded
with decreased GH release exhibited increased CVD of lysosomes after incubation with somatostatin or SMS 201–995. These results
indicate that both densely and sparsely granulated somatotroph adenomas respond to somatostatin inhibition and, furthermore,
that inhibition of hormone release is associated with accumulation of lysosomes, suggesting lysosomal degradation of stored
hormone.
Hospital 20 Nov. (ISSSTE) Coyoacan y Felix Cuevas, Colonia del Valle and (Dept Patologia) y Hospital de Especialidades (C.M.N.,
IMSS) Cuauhtemoc y Dr. Marquez, Mexico City (IF). 相似文献
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Chromosome 11 numerical abnormalities were detected by fluorescencein situ hybridization (FISH) technique in four surgically removed pituitary somatotroph adenomas from patients clinically associated
with acromegaly. The tumors were diagnosed by histology, immunocytochemistry, and electron microscopy, and included two densely
granulated somatotroph (DG-SM) and two sparsely granulated somatotroph (SG-SM) adenomas. For demonstration of chromosome 11,
the direct FISH technique was applied on imprints from fresh adenoma tissue fixed in acetone using an α-satellite specific
centromeric probe. The slides were studied with a fluorescence microscope and the percentages of positive nuclei with aberrant
fluorescent signals were counted. All tumors exhibited numerical chromosomal abnormalities in 8–23% of their cell population
and included nuclei containing 1–3 extra chromosome 11 copies. The SG-SM adenomas exhibited more prominent abnormalities compared
with the DG-SM adenomas. We conclude that numerical chromosome 11 abnormalities represent a frequent event among somatotroph
adenomas with a tendency for higher frequency in SG-SM adenomas. 相似文献
11.
Shunichi Yokoyama Kamal Thapar Kalman Kovacs L. Stefaneanu 《Virchows Archiv : an international journal of pathology》1998,432(3):241-246
Insulin-like growth factors (IGFs) have been reported to promote cell proliferation in many tumours, but their contribution to pituitary adenoma development and growth has not been characterized. We report the presence of insulin-like growth factor II (IGF-II) mRNA in pituitary adenomas using in situ hybridization (ISH). The intensity of IGF-II hybridization signal was correlated with adenoma type, and the presence of Ki-67. Among the 109 adenomas examined, 55 (50.4%) were positive for IGF-II mRNA. All acidophil stem cell, functioning corticotrophic and plurihormonal adenomas contained the message; a high incidence of signal was found among sparsely (7/8) and densely (4/6) granulated growth hormone (GH) cell adenomas, mixed GH cell–prolactin (PRL) cell adenomas (6/7), thyrotrophic (4/6) and null-cell (6/7) adenomas. Less frequently, IGF-II mRNA was localized in mammosomatotrophic, silent subtype 3, gonadotrophic, and oncocytic adenomas, whereas all sparsely granulated PRL cell adenomas and silent corticotrophic adenomas of subtypes 1 and 2 were negative. The MIB-1 labelling index was significantly higher in adenomas with a moderate to intense IGF-II signal than in adenomas with weak or no signal. The results suggest that IGF-II, when highly expressed, may have a role in pituitary adenoma proliferation. 相似文献
12.
Akiko Yoneda Toshiaki Sano Shozo Yamada Abdulkader Obari Zhi Rong Qian Elaine Lu Wang Naoko Inosita Eiji Kudo 《Endocrine pathology》2010,21(1):40-47
Growth hormone (GH)-producing pituitary adenomas have been classified into densely and sparsely granulated adenomas. The latter
are chromophobic with weak GH-positivity and characteristically possess fibrous body (FB), aggregation of cytokeratin filaments.
We report eight cases of unusual chromophobic adenomas. GH-immunoreactivity was detected in most adenoma cells in five cases
and scattered in three cases. However, it appeared much weaker than that seen in ordinary GH-producing adenomas because of
spotty immunoreactivity. Although intracytoplasmic organelles were well-developed, secretory granules were small and sparse.
FB was not identified in any cases. Thyroid-stimulating hormone was positive in four cases. Pit-1 protein was positive in
all eight cases. A weak labeling with GH probe was detected in two of two cases examined by in situ hybridization. Acromegalic
features were evident in four cases, while mild or absent in four cases. GH levels were below 5 μg/l in four cases and 5–10 μg/l
in the remaining cases. Macroadenomas and invasive adenomas were seen in seven and six cases, respectively. 相似文献
13.
Acidophil stem cell adenoma of the human pituitary. 总被引:2,自引:0,他引:2
E Horvath K Kovacs W Singer C Ezrin N A Kerenyi 《Archives of pathology & laboratory medicine》1977,101(11):594-599
Among 87 pituitary adenomas, four neoplasms had a superficial resemblance to undifferentiated cell adenomas and some fine structural features of both sparsely granulated adenomatous growth hormone and prolactin cells. Misplaced exocytosis, fibrous bodies, and multiple centrioles were sometimes revealed within the same cell and usually were accompanied by oncocytic transformation, mitochondrial alterations, and abnormal centriologenesis. The patients had normal or low blood growth hormone levels and elevated or normal prolactin values. All the tumors that were tested contained immunoreactive growth hormone and prolactin, irrespective of the blood hormone levels. The four tumors could represent a hitherto unclassified adenoma type and derive from the common, committed precursor of the two acidophils. The term acidophil stem cell adenoma is proposed to designate this entity. 相似文献
14.
Michael Schmid Adrian Münscher Wolfgang Saeger Silke Schreiber Dieter K. Lüdecke 《Pathology, research and practice》2001,197(10):663-669
Null cell adenomas and oncocytomas are clinically inactive adenomas of the pituitary gland. They do not show any significant hormone content detectable by immunohistochemistry. This study aimed at demonstrating mRNAs for all main pituitary hormones in 32 null cell adenomas and 31 oncocytomas by non-isotopic in situ hybridization using digoxigenin-labeled oligonucleotide probes. The results were compared with immunohistochemical and clinical data. Immunohistochemistry (ABC method) was done with monoclonal antibodies against PRL, GH, FSH, LH, TSH, ACTH, alpha-subunit, and Ki-67 (mib-1). The signals for hormone production were detected in both adenoma types in a range from 42% for GH in oncocytomas to 78% for beta-FSH in null cell adenomas. However, these signals are apparently not effective on hormone production, as was shown by almost negative immunostaining. Owing to the simultaneous detection of at least two mRNAs in 78% of null cell adenomas and in 94% of oncocytomas, we assume that both tumor types originate from pluripotential precursor cells that are capable of producing various hormones. According to our data, it is unlikely that the signals influence the clinical behavior. 相似文献
15.
Growth hormone (GH) and prolactin (PRL) gene expression and immunoreactivity in GH- and PRL-producing human pituitary adenomas 总被引:3,自引:0,他引:3
Jie Li Lucia Stefaneanu Kalman Kovacs Eva Horvath Harley S. Smyth 《Virchows Archiv : an international journal of pathology》1993,422(3):193-201
Summary Growth hormone(GH)-producing pituitary adenomas are morphologically heterogeneous and frequently contain not only GH immunoreactivity but also variable numbers of prolactin (PRL) immunopositive cells. Paraffin sections of 59 surgically removed GH- and/or PRL-producing adenomas classified by histology, immunocytochemistry (ICC) and electron microscopy were studied using in situ hybridization (ISH) for GH and PRL mRNA and combined with ICC for the coded hormones. Somatotroph adenomas (10 densely and 10 sparsely granulated tumours) and mammosomatotroph adenomas (10 cases) contained both GH mRNA and GH immunoreactivity. In 4 densely and 4 sparsely granulated somatotroph adenomas and 4 mammosomatotroph adenomas, only GH mRNA and its product were found. In 28 cases (6 densely and 6 sparsely granulated somatotroph adenomas, 10 mixed somatotrophlactotroph adenomas and 6 mammosomatotroph adenomas) both GH and PRL mRNA were present, although no PRL immunoreactivity was not in 2 densely granulated somatotroph adenomas. In these cases, ISH for PRL mRNA combined with GH immunostaining revealed the presence of variable numbers of mammosomatotrophs. In 9 acidophil stem cell adenomas only PRL mRNA and its product were found; one tumour expressed both GH and PRL mRNA and their products. Nine lactotroph adenomas contained only PRL mRNA and PRL immunoreactivity. The results show that GH and/or PRL mRNA content could not be correlated with ICC for coded proteins and ultrastructural features. The mammosomatotrophs were more numerous using ISH when compared with ICC. Somatotroph, mammosomatotroph and mixed adenomas are closely related and they can be considered to represent one basic tumour type originating in a cell committed to GH production. This may undergo clonal differentiation towards a mammosomatotroph and further to the lactotroph line. The results also indicate that lactotroph adenomas arise in a cell committed to PRL production. Acidophil stem cell adenomas seem to be more closely related to lactotroph cells than somatotroph. 相似文献
16.
Octreotide, a somatostatin analog used to treat acromegalic patients harboring a pituitary tumor, acts via somatostatin subtype
2 receptor (SSTR2) and causes significant decrease of circulating GH levels and sometimes mild to moderate tumor shrinkage.
To further elucidate the mechanism of octreotide action, we studied GH and SSTR2 mRNAs by in situ hybridization in densely and sparsely granulated somatotroph adenomas removed by surgery from 14 treated and 14 untreated
patients. Only in densely granulated adenomas were the GH and SSTR2 mRNA signals mildly decreased relative to untreated matched
adenomas. The decrease of GH mRNA in densely granulated somatotroph adenomas suggests that they may have a more favorable
response to octreotide therapy than sparsely granulated tumors. 相似文献
17.
Shigeyuki Tahara Reiko Kurotani Yudo Ishii Naoko Sanno Akira Teramoto R Yoshiyuki Osamura 《Modern pathology》2002,15(10):1102-1105
18.
Toshiko Sumi Lucia Stefaneanu Kalman Kovacs Sylvia L. Asa Guido Rindi 《Endocrine pathology》1993,4(2):95-99
In many human cancers, p53 gene mutations are frequently occurring genetic abnormalities, which may be detected by immunohistochemical
staining for p53 protein. In the present study, p53 immunoreactivity was investigated in formalin-fixed, paraffin-embedded
tissues from human and animal pituitary tumors, using the avidin-biotin-peroxidase complex technique. No p53 was detected
in 3 nontumorous human adenohypophyses or in 40 human pituitary tumors including 5 GH cell adenomas, 10 PRL cell adenomas,
2 mixed GH cell-PRL cell adenomas, 2 acidophil stem cell adenomas, 8 ACTH cell adenomas, 1 TSH cell adenoma, 1 FSH/LH cell
adenoma, 5 null cell adenomas, 5 oncocytomas, and 1 plurihormonal adenoma. Twenty nontumorous and hyperplastic pituitaries
of hGRH transgenic mice and 8 tumors in these transgenic animals were immunonegative for p53. All pituitary tumors found in
AVP/SV40 transgenic mice contained p53 immunoreactivity in the nuclei, while the nontumorous adenohypophysis of one such transgenic
mouse was negative. It can be concluded that p53 mutations are apparently not involved in the pathogenesis of human pituitary
adenomas or of the pituitary tumors which develop in hGRH transgenic mice. However, pituitary tumors in AVP/ SV40 transgenic
mice are accompanied by p53 expression. 相似文献
19.
Molecular cytogenetics of chromosome 11 in pituitary adenomas: a comparison of fluorescence in situ hybridization and DNA ploidy study 总被引:2,自引:0,他引:2
Chromosome 11 abnormalities were detected by fluorescence in situ hybridization (FISH) technique and compared with DNA ploidy in 24 surgically removed pituitary adenomas. The tumors were diagnosed and classified by histology, electron microscopy, and pituitary hormone immunocytochemistry. They included 2 densely granulated somatotroph (DG-SM) and 4 sparsely granulated somatotroph (SG-SM) adenomas, 3 SG lactotroph (LT), 2 mixed somatotroph-lactotroph (SM-LT), 4 functioning corticotroph (CRT), 1 silent CRT subtype 1, 1 thyrotroph, 1 mixed thyrotroph-somatotroph, 2 gonadotrophs, and 4 null cell adenomas. FISH analysis with an alpha-satellite DNA probe specific for chromosome 11 showed numerical abnormalities in 16 functioning (94%) and 5 nonfunctioning (71%) adenomas. Ten functioning tumors showed aneuploid histograms, whereas the remaining and all nonfunctioning adenomas were diploid. Aberrant chromosome 11 signals were noted mostly in aneuploid adenomas involving 17% to 100% of their cell population. The severity of chromosome 11 aberrations in adenomas containing extra copies often correlated with a higher DNA index (DI). Monosomy 11 as dominant aberration was noted in a mixed SM-LT and to a lesser degree in 3 CRT adenomas involving 21% to 97% of their cell population. Two of these CRT adenomas were associated with normal DI, whereas the remaining third showed a high DI, indicating increased copy number of chromosomes other than of chromosome 11. In conclusion, chromosome 11 abnormalities are common in all types of pituitary adenomas, occurring more frequently in functioning tumors. Specific numerical abnormalities, such as monosomy and trisomy, tend to be associated with certain adenoma types, whereas tumors with extra chromosome 11 copies often exhibit aneuploid histograms. 相似文献
20.
This paper reviews the morphologic features of growth hormone-producing tumors of the human pituitary. These tumors are associated with elevated blood growth hormone levels and acromegaly or gigantism and can be classified into the following morphologically distinct entities by the combined application of histology, immunocytology, and electron microscopy: densely granulated growth hormone cell adenoma; sparsely granulated growth hormone cell adenoma; mixed growth hormone cell- prolactin cell-adenoma; acidophil stem cell adenoma; mammosomatotroph cell adenoma; growth hormone cell carcinoma; plurihormonal adenoma with growth hormone production. 相似文献